Overview
This lecture covers the E2 elimination reaction mechanism, rate law, stereochemical requirements, product prediction (Zaitsev vs. Hofmann), and special scenarios involving cyclohexanes, bulky bases, and poor leaving groups.
E2 Reaction Mechanism
- E2 stands for elimination bimolecular, involving two molecules in the rate-determining step: a strong base and the substrate (alkyl halide).
- The base removes a β-hydrogen, forming a double bond as the leaving group exits simultaneously (concerted, single-step process).
- Most strong bases in E2 are negatively charged oxygens (e.g., NaOH, NaOCH₃).
E2 Rate Law
- E2 has a rate law: rate = k[base][substrate], first order in each, second order overall.
- Reaction rate doubles if either base or substrate concentration is doubled.
Stereochemical Requirements
- E2 eliminations require the hydrogen and leaving group to be anti-periplanar (almost 180° apart).
- The reaction "locks" the product into the conformation present during elimination, affecting whether a cis (Z) or trans (E) alkene forms.
- If only one β-hydrogen is present, only one E/Z isomer is possible.
Predicting Major Products: Zaitsev vs. Hofmann
- Zaitsev's rule: the most substituted (more stable) alkene is usually the major E2 product.
- Exceptions occur: if conformation prevents elimination at the more substituted carbon or with certain bases/leaving groups.
E2 on Cyclic Systems (Cyclohexane)
- Free rotation is limited; only axial hydrogens trans to axial leaving groups can be eliminated.
- Only the chair conformation with axial leaving groups and axial trans β-hydrogens is reactive.
- Often, the less substituted alkene (Hofmann product) is formed if only accessible hydrogen is on a less substituted carbon.
Bulky Bases and Hofmann Product
- Bulky bases (e.g., potassium t-butoxide) favor deprotonation at less hindered, less substituted β-carbons, forming the Hofmann product.
- For most, memorize: bulky base → Hofmann (less substituted) product.
Poor Leaving Group Effects
- Poor leaving groups (e.g., fluoride) also favor the Hofmann product due to a carbanion-like transition state, which is more stable on less substituted carbons.
Key Terms & Definitions
- E2 Reaction — A bimolecular elimination where base and substrate react in one concerted step.
- Zaitsev Product — The more substituted, stable alkene formed in elimination.
- Hofmann Product — The less substituted alkene, major product with bulky base or poor leaving group.
- Anti-Periplanar — Hydrogen and leaving group are nearly 180° apart, necessary for E2.
- Bulky Base — Large, sterically hindered base (e.g., t-butoxide).
- Concerted Mechanism — All bond breaking and forming occur in one step.
Action Items / Next Steps
- Practice drawing E2 mechanisms with attention to stereochemistry.
- Memorize Zaitsev vs. Hofmann product prediction rules.
- Review cyclohexane chair conformations for E2 reactions.
- Complete assigned practice problems or quizzes as directed.